We propose the development of a low-cost, fully automated DNA/RNA Array Synthesizer to efficiently generate large-scale, high-density DNA/RNA chips for diagnosis, sequence analysis, drug discovery, medical, and bioassay applications. The proposed project will advance biochip fabrication technologies by providing solutions to the existing problems on technology accessibility, flexibility, and product purity. Two innovations will be implemented: A novel solution photochemistry allows well established conventional synthesis protocols to be used in DNA/RNA synthesis with light-directed parallel processes and at high stepwise yields. A programmable, maskless photolithographic system provides the flexibility for making custom DNA/RNA chips of any desirable sequence designs. The proposed Phase I research will lead to successful applications of the two innovations. Phase II investigations will result in a prototype automated DNA/RNA Array Synthesizer that enables large-scale, high- density, high-fidelity custom DNA/RNA-chips to be made at low costs. The first set of the DNA/RNA-chips will target mutation detection in human disease genes, such as p53, ovarian and breast cancer genes. Our longer- term goals are to provide array synthesizers that can be routinely operated in research laboratories and to massively produce high-fidelity, low cost combinatorial biochips for medical research and diagnostic/screening applications. PROPOSED COMMERCIAL APPLICATION: The new DNA/RNA Array Synthesizer will, for the first time, allow any researcher in the field to make large-scale, high-density, and high- fidelity DNA/RNA-chips of their own design and at an affordable price. The instrument will be used in research laboratories of pharmaceutical companies, medical research institutions, and universities for drug discoveries, DNA diagnosis, and gene analysis. The technology developed in the proposed effort has the potential to be extended to other types of combinatorial library microassays, such as those containing peptides and carbohydrates, which, thus far, cannot be made on a commercial scale.